Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways
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Mitsuho Imai-Sumida1, Takeshi Chiyomaru1,2, Shahana Majid1, Sharanjot Saini1, Hannah Nip1, Rajvir Dahiya1, Yuichiro Tanaka1 and Soichiro Yamamura1
1Department of Urology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA, USA
2Current address: Department of Urology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
Soichiro Yamamura, email: Soichiro.Yamamura@ucsf.edu
Yuichiro Tanaka, email: Yuichiro.Tanaka@ucsf.edu
Keywords: silibinin, bladder cancer, KRAS, PI3K, long non-coding RNA
Received: October 07, 2016 Accepted: August 07, 2017 Published: September 08, 2017
Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been studied extensively. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation, migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide 3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines. These pathways were found to crosstalk through RAS cascades. We found that silibinin suppressed levels of trimethylated histone H3 lysine 4 and acetylated H3 at the KRAS promoter. Furthermore, silibinin targets long non-coding RNA: HOTAIR and ZFAS1, which are known to play roles as oncogenic factors in various cancers. This study shows that silibinin exerts anti-cancer effects through down-regulation of actin cytoskeleton and PI3K/Akt pathways and thus suppresses bladder cancer growth and progression.
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